Twist on Pain Drug Improves Heart Attack Outcome

Periannan Kuppusamy, professor of internal medicine at Ohio State University and colleagues treated rat hearts with trimetazidine (TMZ), a drug given to people with angina, or severe, chronic chest pain. TMZ is an anti-ischemic drug, meant to decrease oxygen use and reduce tissue damage caused by the blockage of blood flow, or ischemia, in vessels. The researchers created two new forms, or derivatives, of TMZ by combining the drug with one of two types of chemical-based antioxidants. They called the derivatives TMZ-NH and TMZ-FNH.

Hearts were surgically removed from the rats. The researchers then placed each heart in its own small glass tube, and continuously injected, or perfused, a solution of nutrients through the hearts to keep them pumping. Rat hearts were separated into four groups: one group received TMZ only, another group received TMZ-NH, and the hearts in the last treatment group were treated with TMZ- FNH. Rat hearts used as controls weren’t treated with any medication.

Results showed that pre-treatment with the derivatives TMZ-NH and TMZ-FNH was most effective at protecting hearts from injury by subsequent reperfusion. TMZ alone offered some protection from tissue damage during reperfusion, but not to the degree of the antioxidant derivatives.

Free-radical levels were about 50 percent higher in both the control hearts and rat hearts treated with TMZ, compared to the level in hearts treated with the antioxidant derivatives. Also, the area of irreversible tissue damage, called an infarct, was substantially smaller – about half the size – in the hearts treated with the antioxidants.

“These hearts were stronger and healthier overall – they were better able to contract and therefore better able to accommodate the flow of the solution during reperfusion,” Kuppusamy said. “Combining antioxidants with a drug already used to treat ischemia could be an efficient way to improve the outcome of a heart attack.”